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Vonoprazan Fumarate Shows Promise for Treatment of Acid-Related Diseases

Phase III data demonstrate non-inferiority to lansoprazole

Positive results from five phase III trials of vonoprazan fumarate (TAK-438, Takeda) were presented at Digestive Disease Week, held May 3–6 in Chicago.

Vonoprazan fumarate belongs to a new class of acid-secretion inhibitors called potassium-competitive acid blockers (P-CABs). The drug competitively inhibits the binding of potassium ion to H+, K+-ATPase (proton pump) in the final step of gastric acid secretion in gastric parietal cells.

The first phase III trial compared the efficacy and safety of TAK-438 (20 mg once daily) with that of lansoprazole (LPZ) (30 mg once daily) in 409 Japanese patients with erosive esophagitis (EE). For the primary endpoint — the proportion of healed patients at week 8 — the non-inferiority of TAK-438 to LPZ was verified (99.0% vs. 95.5%, respectively; P < 0.0001). The superiority of TAK-438 to LPZ was also verified for the proportion of healed patients at week 8 based on the results of a post hoc analysis (P = 0.0337).

The second study evaluated the efficacy and safety of TAK-438 (10 mg or 20 mg once daily) compared with that of LPZ (15 mg once daily) in 24-week maintenance treatment of healed EE in 607 patients. For the primary endpoint — the proportion of patients with recurrence at week 24 — non-inferiority to LPZ was verified for both TAK-438 treatment groups. The results were 16.8%, 5.1%, and 2.0% in the LPZ 15-mg, TAK-438 10-mg, and TAK-438 20-mg groups, respectively (P < 0.0001 for TAK-438 vs. LPZ). Superiority to LPZ was also verified for both TAK-438 groups for the proportion of patients with recurrence at week 24 based on a post hoc analysis (LPZ 15 mg vs. TAK-438 10 mg, P = 0.0002; LPZ 15 mg vs. TAK-438 20 mg, P < 0.0001).

The third trial evaluated the efficacy and safety of TAK-438 (10 mg or 20 mg once daily) compared with that of LPZ (15 mg once daily) for secondary prevention of peptic ulcers associated with treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) in 642 patients. At week 24, the non-inferiority of TAK-438 10 mg and 20 mg to LPZ 15 mg was verified for the proportion of patients with recurrent peptic ulcers (LPZ 15 mg, 5.5%; TAK-438 10 mg, 3.3%; and TAK-438 20 mg, 3.4% [P < 0.0001 vs. LPZ]). The proportion of patients with recurrent peptic ulcers in the TAK-438 10-mg and 20-mg groups through week 24 was slightly lower than in the LPZ 15-mg group, but no statistically significant differences were observed. The proportion of cumulative incidences of gastric ulcer, duodenal ulcer, or hemorrhagic lesion was lower in each TAK-438 group than in the LPZ group.

The fourth study evaluated the efficacy and safety of TAK-438 (10 mg or 20 mg once daily) compared that of LPZ (15 mg once daily) for secondary prevention of peptic ulcers associated with low-dose aspirin (LDA) therapy in 621 patients. At week 24, the non-inferiority of TAK-438 10 mg and 20 mg to LPZ 15 mg was verified for the proportion of patients with recurrent peptic ulcers (LPZ 15 mg, 2.8%; TAK-438 10 mg, 0.5%; TAK-438 20 mg, 1.5% [P < 0.0001 vs. LPZ]). The proportion of patients with recurrent peptic ulcers in the TAK-438 10-mg and 20-mg groups through 24 weeks was slightly lower than in the LPZ group, although no statistically significant differences were observed.

The fifth trial evaluated the efficacy and safety of triple therapy with TAK-438, amoxicillin, and clarithromycin for first-line eradication of Helicobacter pylori compared with that of triple therapy with LPZ, amoxicillin, and clarithromycin in 650 patients. In an analysis of the primary endpoint — the H. pylori eradication rate — the non-inferiority of first-line therapy with TAK-438 compared with LPZ was verified using the Farrington and Manning test, with a non-inferiority margin of 10% (eradication rates: TAK-438, 92.6% vs. LPZ, 75.9%; P < 0.0001).

Source: Takeda; May 7, 2014.

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